Lactate does not activate the carotid body of Wistar rat

Spiller, Pedro F.; Silva, Melina P. da; Moraes, Deovaldo de

doi:10.1016/j.resp.2020.103593

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…2b). It has recently been reported that membrane potential and conductance of rat glomus cells are unaffected by lactate, however, these experiments were performed with the whole-cell configuration of the patch-clamp technique and therefore intracellular dialysis may have altered the lactate signaling pathway 37…”

Section: Resultsmentioning

confidence: 99%

Lactate sensing mechanisms in arterial chemoreceptor cells

et al. 2021

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Classically considered a by-product of anaerobic metabolism, lactate is now viewed as a fundamental fuel for oxidative phosphorylation in mitochondria, and preferred over glucose by many tissues. Lactate is also a signaling molecule of increasing medical relevance. Lactate levels in the blood can increase in both normal and pathophysiological conditions (e.g., hypoxia, physical exercise, or sepsis), however the manner by which these changes are sensed and induce adaptive responses is unknown. Here we show that the carotid body (CB) is essential for lactate homeostasis and that CB glomus cells, the main oxygen sensing arterial chemoreceptors, are also lactate sensors. Lactate is transported into glomus cells, leading to a rapid increase in the cytosolic NADH/NAD+ ratio. This in turn activates membrane cation channels, leading to cell depolarization, action potential firing, and Ca2+ influx. Lactate also decreases intracellular pH and increases mitochondrial reactive oxygen species production, which further activates glomus cells. Lactate and hypoxia, although sensed by separate mechanisms, share the same final signaling pathway and jointly activate glomus cells to potentiate compensatory cardiorespiratory reflexes.

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Section: Resultsmentioning

confidence: 99%

Lactate sensing mechanisms in arterial chemoreceptor cells

et al. 2021

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“…The specific role of each mediator could be dependent on the specific intensity of hypoxia as has been suggested for release of neurotransmitters/neuromodulators [ 43 ]. That said, there are questions over a role of lactate being involved in CB O 2 sensing in the rat based on the recent finding that acute lactate administration (up to 20 mM) does not evoke type I cell depolarisation or chemoafferent excitation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Succinate Metabolism and Reactive Oxygen Species Are Important but Not Essential for Eliciting Carotid Body and Ventilatory Responses to Hypoxia in the Rat

et al. 2021

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Reflex increases in breathing in response to acute hypoxia are dependent on activation of the carotid body (CB)—A specialised peripheral chemoreceptor. Central to CB O2-sensing is their unique mitochondria but the link between mitochondrial inhibition and cellular stimulation is unresolved. The objective of this study was to evaluate if ex vivo intact CB nerve activity and in vivo whole body ventilatory responses to hypoxia were modified by alterations in succinate metabolism and mitochondrial ROS (mitoROS) generation in the rat. Application of diethyl succinate (DESucc) caused concentration-dependent increases in chemoafferent frequency measuring approximately 10–30% of that induced by severe hypoxia. Inhibition of mitochondrial succinate metabolism by dimethyl malonate (DMM) evoked basal excitation and attenuated the rise in chemoafferent activity in hypoxia. However, approximately 50% of the response to hypoxia was preserved. MitoTEMPO (MitoT) and 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SKQ1) (mitochondrial antioxidants) decreased chemoafferent activity in hypoxia by approximately 20–50%. In awake animals, MitoT and SKQ1 attenuated the rise in respiratory frequency during hypoxia, and SKQ1 also significantly blunted the overall hypoxic ventilatory response (HVR) by approximately 20%. Thus, whilst the data support a role for succinate and mitoROS in CB and whole body O2-sensing in the rat, they are not the sole mediators. Treatment of the CB with mitochondrial selective antioxidants may offer a new approach for treating CB-related cardiovascular–respiratory disorders.

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“…It is currently under discussion whether chemoreceptors can detect lactate; therefore, the ventilatory response during exercise could be related to CB activation (Chang et al, 2015;Torres-Torrelo et al, 2021). Nevertheless, it has been shown that CB chemoreceptor cells do not respond to lactate in Wistar Kyoto rats (Spiller et al, 2021). In summary, during an incremental exercise, there is a complex, highly coordinated physiological mechanism encompassing pulmonary, Frontiers in Physiology frontiersin.org cardiovascular, metabolic, and autonomic responses that enable the proper delivery of O 2 to the active tissues.…”

Section: Reciprocal Relationship Between Exercise and Hypoxic Chemore...mentioning

confidence: 99%

Baroreflex and chemoreflex interaction in high-altitude exposure: possible role on exercise performance

Alvarez-Araos,

Jiménez,

Salazar-Ardiles

et al. 2024

Front. Physiol.

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The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure.

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Lactate does not activate the carotid body of Wistar rat

Cited by 7 publications

References 37 publications

Lactate sensing mechanisms in arterial chemoreceptor cells

Lactate sensing mechanisms in arterial chemoreceptor cells

Mitochondrial Succinate Metabolism and Reactive Oxygen Species Are Important but Not Essential for Eliciting Carotid Body and Ventilatory Responses to Hypoxia in the Rat

Baroreflex and chemoreflex interaction in high-altitude exposure: possible role on exercise performance

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